1. Field Of The Invention
This invention relates to a flow cytometer, and more particularly, to a flow cytometer having the capability of processing signal voltages ranging over at least four orders of magnitude and for detecting new signals prior to completing the processing of previously detected signals.
2. Description of the Prior Art
Flow cytometer systems are common medical laboratory instruments used to perform an analysis of many different cell types, including blood cells. For example, they are commonly used to count and differentiate between various types of blood cells, particularly sub-types of white blood cells. Generally, conventional flow cytometer systems, utilize a narrow columnar stream of fluid formed to contain the cells to be examined. This stream passes through a flow cell having a window through which a light beam, such as from a laser, is passed. When a cell intersects the light beam, light is scattered in the forward direction which is proportional to the size of the cell, and at wide angles from the smaller structures of the cell. Generally, the cells being examined will previously have been treated with fluorescent dyes or markers connected to fluorescent dyes, and after being placed in the light path, different cells will emit different fluorescent color and intensity light patterns. Particular cells can be identified by observing both the effect of the light scattered from the cell, such as the amount of light scattered at various angles, as well as the various fluorescent light patterns.
Examples of various prior art flow cytometer systems are shown in U.S. Pat. No. 3,380,584 granted Apr. 30, 1968 to M. J. Fulwyler and entitled "Particle Separator"; U.S. Pat. No. 3,657,537, granted Apr. 18, 1972 in the name of L. L. Wheeless, Jr. et al and entitled, "Computerized Slit-Scan Cytofluorometer For Automated Cell Recognition"; U.S. Pat. No. 4,038,556 granted Jul. 26, 1977 in the name of Robert E. Auer et al and entitled, "Method and Apparatus For Simultaneous Optical Measurements of Particle Characteristics"; U.S. Pat. No. 4,348,107, granted Sep. 7, 1982 in the name of Robert C. Leif and entitled, "Orifice Inside Optical Element"; U.S. Pat. No. 4,467,830, granted May 26, 1987 in the name of Tom Nozaki, Jr. et al and entitled, "Method And Means For Sorting Individual Particles Into Containers For Culturing, Cloning Analysis Or The Like"; and U.S. Pat. No. 4,778,593, granted Oct. 18, 1988 in the name of Mikio Yamashita et al and entitled, "Method And Apparatus For Discriminating Minute Particles".
The existing prior art flow cytometer machines have several shortcomings, due primarily to the large variance in the scatter and fluorescence signals that are to be measured. This variance results in voltage signals over many orders of magnitude, all of which must be processed in order to identify the particular cell types. For example, the voltage pulses obtained, after initially setting the machine, can vary from less than five millivolts to more than ten volts. State of the art analog electronic components cannot adequately handle voltage variations over this range in performing analog subtractive normalization techniques and log amplification. These analog electronic components are highly sensitive to thermal drift effects and have bandwidth limitations for pulse detection applications. Another problem with existing flow cytometer machines is that the time to process the signal information limits the rate at which cells can be detected. This latter problem, in turn, increases the time for performing a differential analysis of the cells in a given sample. A need exists to solve both of these problems.